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Background Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Methods This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load

Exposure to violence in childhood has been linked to adverse health outcomes. Little is known about the prevalence and relationship of youth and caregiver violence exposure to clinical outcomes among youth with perinatal human immunodeficiency virus (HIV) infection (PHIV). We evaluated associations of youth and caregiver violence exposure with unsuppressed viral load (VL) (HIV RNA400 copies/mL) and CD4%25% among 8- to 15-year-old participants with PHIV in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol.Annual clinical examination, record abstraction, and interview data were collected, including youth report of recent exposure to violence and caregivers' self-report of being assaulted/abused in adulthood. Multivariable logistic regression methods were used to calculate adjusted odds ratios for unsuppressed VL and CD4%25%, controlling for sociodemographic characteristics.Among 268 youth with PHIV (53% girls, mean age 12.8 years, 21% white, 42% with household income$20,000/year), 34% reported past year violence exposure; 30% had a caregiver who reported being assaulted in adulthood. One quarter of youth (24%) had unsuppressed VL and 22% had CD4%25%. Youth who were exposed to violence in the past year versus those who were not had elevated odds of unsuppressed VL. Youth with indirect exposure to violence in the past year versus those without had elevated odds of unsuppressed VL and CD4%25% in adjusted models.Youth with PHIV report a high prevalence of recent violence exposure, which was associated with poor virologic and immunologic outcomes. Reducing violence and providing support to youth with violence exposure and PHIV may improve health outcomes.

Among 234 US youths with perinatal human immunodeficiency virus, 75% had antiretroviral resistance, substantially higher than that of the reference laboratory overall (36%-44%). Resistance to newer antiretrovirals and to all antiretrovirals in a class was uncommon. The only factor independently associated with future resistance was a higher peak viral load.

Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18–24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n = 56); group 2 had CD4 >350 and were not initiating ART (n = 66); group 3 initiated ART with CD4

Although human papillomavirus (HPV) infections are common in HIV-infected adults, little is known about children. Our objective was to examine the prevalence of and risks for HPV of the oral mucosal and external genital areas in nonsexually active (NSA) perinatally (P) HIV+ children and compare with HIV-exposed but uninfected (HEU) children. A convenience sample attending a pediatric clinic were enrolled. Samples for HPV were obtained from the oral and anogenital areas and tested for one of 37 HPV types. The mean age of the 48 PHIV+ children was 14.3±3.9 years vs. 6.2±4.8 for the 52 HEU (p

Purpose Youth living with human immunodeficiency virus (HIV) account for over one third of new HIV infections and are at high risk of adverse psychosocial, everyday living, and health outcomes. Human immunodeficiency virus–associated neurocognitive disorders (HAND) are known to affect health outcomes of HIV-infected adults even in the era of combination antiretroviral therapy. Thus, the current study aimed to characterize the prevalence and clinical correlates of HAND in youth living with HIV. Here, we report baseline neurocognitive data for behaviorally HIV-infected youth enrolled in a prospective study evaluating strategies of antiretroviral treatment initiation and use. Methods A total of 220 participants, age 18–24 years, who were naive to treatment (except for prevention of mother-to-child HIV transmission; n = 3), completed a comprehensive neurocognitive, substance use, and behavioral health assessment battery. Results Sixty-seven percent of youth met criteria for HAND (96.4% were asymptomatic and 3.5% were syndromic); deficits in episodic memory and fine-motor skills emerged as the most commonly affected ability areas. Multivariable models showed that lower CD4 count, longer time since HIV diagnosis, and high-risk alcohol use were uniquely associated with neurocognitive deficits. Conclusions Over two thirds of youth with behaviorally acquired HIV evidence neurocognitive deficits, which have modest associations with more advanced HIV disease as well as other factors. Research is needed to determine the impact of such neuropsychiatric morbidity on mental health and HIV disease treatment outcomes (e.g., nonadherence) and transition to independent living responsibilities in HIV-infected youth, as well as its long-term trajectory and possible responsiveness to cognitive rehabilitation and pharmacotherapy.

Introduction The first generation of adolescents born with HIV infection has reached young adulthood due to advances in treatment. It is important to continue follow-up of these individuals to assess their long-term medical, behavioural and mental health and ability to successfully transition to adulthood while coping with a chronic, potentially stigmatising condition. To accomplish this, and to maintain their interest in long-term research participation, we need to accommodate the changing lifestyles and interests of young adult study participants while ensuring valid data collection. We report the protocol for Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) Up, a prospective cohort study enrolling young adult participants for long-term follow-up. Methods and analysis AMP Up is recruiting 850 young men and women 18 years of age and older—600 perinatally HIV-infected and a comparison group of 250 perinatally HIV-exposed, uninfected—at 14 clinical research sites in the USA and Puerto Rico. Recruitment began in April 2014 and is ongoing, with 305 participants currently enrolled. Planned follow-up is ≥6 years. Data are collected with a flexible hybrid of online and in-person methods. Outcomes include: transition to adult clinical care and retention in care; end-organ diseases; malignancies; metabolic complications; sexually transmitted infections; reproductive health; mental health and neurocognitive functioning; adherence to antiretroviral treatment; sexual behaviour and substance use; hearing and language impairments; and employment and educational achievement. Ethics and dissemination The study received ethical approval from the Harvard T.H. Chan School of Public Health9s institutional review board (IRB), and from the IRBs of each clinical research site. All participants provide written informed consent; for cognitively impaired individuals with legally authorised representatives, legal guardian permission and participant assent is obtained. Findings will be disseminated through peer-reviewed journals, conference presentations and participant summaries.

Background Increased incidence and prevalence of asthma have been documented for perinatally HIV-infected youth 10 to 21 years of age compared with HIV-exposed uninfected (HEU) youth. Objective We sought to perform objective pulmonary function tests (PFTs) in HIV-infected and HEU youth with and without diagnosed asthma. Method Asthma was determined in 370 participants (218 HIV-infected and 152 HEU participants) by means of chart review and self-report at 13 sites. Interpretable PFTs (188 HIV-infected and 132 HEU participants) were classified as obstructive, restrictive, or normal, and reversibility was determined after bronchodilator inhalation. Values for HIV-1 RNA, CD4 and CD8 T cells, eosinophils, total IgE, allergen-specific IgE, and urinary cotinine were measured. Adjusted prevalence ratios (PRs) of asthma and PFT outcomes were determined for HIV-infected participants relative to HEU participants, controlling for age, race/ethnicity, and sex. Results Current asthma was identified in 75 (34%) of 218 HIV-infected participants and 38 (25%) of 152 HEU participants (adjusted PR, 1.33; P = .11). The prevalence of obstructive disease did not differ by HIV status. Reversibility was less likely in HIV-infected youth than in HEU youth (17/183 [9%] vs 21/126 [17%]; adjusted PR, 0.47; P = .020) overall and among just those with obstructive PFT results (adjusted PR, 0.46; P = .016). Among HIV-infected youth with current asthma, serum IgE levels were inversely correlated with CD8 T-cell counts and positively correlated with eosinophil counts and not associated with CD4 T-cell counts. HIV-infected youth had lower association of specific IgE levels to several inhalant and food allergens compared with HEU participants and significantly lower CD4/CD8 T-cell ratios (suggesting immune imbalance). Conclusion Compared with HEU youth, HIV-infected youth demonstrated decreased reversibility of obstructive lung disease, which is atypical of asthma. This might indicate an early stage of chronic obstructive pulmonary disease. Follow-up into adulthood is warranted to further define their pulmonary outcomes.

Background Children with HIV will be on antiretroviral therapy (ART) longer than adults, and therefore the durability of first-line ART and timing of switch to second-line are key questions. We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line ART and viral load switch criteria in children. Methods In a randomised open-label factorial trial, we compared effectiveness of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30,000 copies per mL in previously untreated children infected with HIV from Europe and North and South America. Random assignment was by computer-generated sequentially numbered lists stratified by age, region, and by exposure to perinatal ART. Primary outcome was change in viral load between baseline and 4 years. Analysis was by intention to treat, which we defined as all patients that started treatment. This study is registered with ISRCTN, number ISRCTN73318385. Findings Between Sept 25, 2002, and Sept 7, 2005, 266 children (median age 6.5 years; IQR 2.8-12.9) were randomly assigned treatment regimens: 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL (PI-low), 65 protease inhibitor and switch at 30,000 copies per mL (PI-higher), 68 NNRTI and switch at 1000 copies per mL (NNRTI-low), and 67 NNRTI and switch at 30,000 copies per mL (NNRTI-higher). Median follow-up was 5.0 years (IQR 4.2-6.0) and 188 (71%) children were on first-line ART at trial end. At 4 years, mean reductions in viral load were -3.16 log(10) copies per mL for protease inhibitors versus -3.31 log(10) copies per mL for NNRTIs (difference -0.15 log(10) copies per mL, 95% CI -0.41 to 0.11; p=0.26), and -3.26 log(10) copies per mL for switching at the low versus -3.20 log(10) copies per mL for switching at the higher threshold (difference 0.06 log(10) copies per mL, 95% CI -0.20 to 0.32; p=0.56). Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group. NNRTI resistance was selected early, and about 10% more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group. Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events; both were balanced across randomised groups. Interpretation Good long-term outcomes were achieved with all treatments strategies. Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited, because the risk of selecting for NRTI and protease-inhibitor resistance is low. Funding Paediatric European Network for Treatment of AIDS (PENTA) and Pediatric AIDS Clinical Trials Group (PACTG/IMPAACT).

Elevated aspartate aminotransferase-to-platelet ratio index (APRI) may signal liver fibrosis. Among 397 US children with perinatal HIV infection, APRI at baseline was > 1.5 in 0.8% (95% confidence interval [CI], 0.2–2.2%) and > 0.5 in 6.5% (95%CI, 4.3–9.4%); incidence on study was 0.5 (95%CI, 0.2–1.2) and 6.4 (95%CI, 4.8–8.3) per 100 person-years, respectively. Long-term liver outcomes after perinatal HIV infection warrant further study.

Two doses of live-attenuated varicella-zoster vaccine are recommended for human immunodeficiency virus 1 (HIV-1)-infected children with CD4% ≥ 15%. We determined the prevalence and persistence of antibody in immunized children with perinatal HIV (PHIV) and their association with number of vaccinations, combination antiretroviral therapy (cART), and HIV status.The Adolescent Master Protocol is an observational study of children with PHIV and perinatally HIV-exposed but uninfected (PHEU) children conducted at 15 US sites. In a cross-sectional analysis, we tested participants' most recent stored sera for varicella antibody using whole-cell and glycoprotein enzyme-linked immunosorbent assay. Seropositivity predictors were identified using multivariable logistic regression models and C statistics.Samples were available for 432 children with PHIV and 221 PHEU children; 82% of children with PHIV and 97% of PHEU children were seropositive (P.001). Seropositivity after 1 vaccine dose among children with PHIV and PHEU children was 100% at3 years (both), 73% and 100% at 3-7 years (P.05), and 77% and 97% at ≥ 7 years (P.01), respectively. Seropositivity among recipients of 2 vaccine doses was94% at all intervals. Independent predictors of seropositivity among children with PHIV were receipt of 2 vaccine doses, receipt of 1 dose while on ≥ 3 months of cART, compared with none (adjusted odds ratio [aOR]: 14.0 and 2.8, respectively; P.001 for overall dose effect), and in those vaccinated ≥ 3 years previously, duration of cART (aOR: 1.29 per year increase, P = .02).Humoral immune responses to varicella vaccine are best achieved when children with PHIV receive their first dose ≥ 3 months after cART initiation and maintained by completion of the 2-dose series and long-term cART use.

Background Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in human immunodeficiency virus (HIV)-related opportunistic infections and deaths in US youth, but both continue to occur. Methods We estimated the incidence of complications and deaths in IMPAACT P1074, a long-term US-based prospective multicenter cohort study conducted from April 2008 to June 2014. Incidence rates of selected diagnoses and trends over time were compared with those from a previous observational cohort study, P219C (2004-2007). Causes of death and relevant demographic and clinical features were reviewed. Results Among 1201 HIV-infected youth in P1074 (87% perinatally infected; mean [standard deviation] age at last chart review, 20.9 [5.4] years), psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections were among the most common comorbid conditions. Compared with findings in P219C, conditions with significantly increased incidence included substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders, and fractures; the incidence of pneumonia decreased significantly. Twenty-eight deaths occurred, yielding a standardized mortality rate 31.5 times that of the US population. Those who died were older, less likely to be receiving cART, and had lower CD4 cell counts and higher viral loads. Most deaths (86%) were due to HIV-related medical conditions. Conclusions Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed.

The onset and time-course of HIV-associated cognitive deficits are not well established. The present experiment compared physiological and neurometric assessments of cognitive decline in HIV-asymptomatic, HIV-symptomatic, and HIV-negative control adult women. The P3 component of standard auditory, event-related electrical potentials of the brain (ERP) and standard neurometric (pencil and paper) test scores were recorded. The P3 ERP measures differentiated both of the clinical HIV groups from the control group. In contrast, the neurometric measures were more sensitive to the difference in cognitive decline between the two clinical groups. It is concluded that both P3 ERP measures and standard neurometric tests are individually useful and complementary for tracking cognitive decline in the diagnosis and treatment of opportunistic HIV-associated central nervous system impairments.

Advances in medical treatment, through combination antiretroviral therapy (ART) and highly active ART (HAART) with protease inhibitors (PIs), have resulted in improved health outcomes among children with human immunodeficiency virus (HIV) infection (DeMartino et al., 2000; Gortmaker et al., 2001). Adherence to HAART regimens is difficult, however, due to the demanding nature of antiretroviral treatment and other unique challenges faced by children and adolescents with HIV and their caregivers. Antiretroviral medications, particularly regimens containing PIs, share characteristics that amplify the inherent difficulties of medication adherence in children and adolescents: poor palatability, heavy pill burden, dietary restrictions, acute and long-term side effects, and restrictions on daily schedules (Reddington et al., 2000; Van Dyke et al., 2002). Children and adolescents with HIV often face other life stressors that affect their ability to achieve adherence, including parental HIV disease, poverty, and limited or inconsistent social support (Steele, Nelson, & Cole, 2007). Adherence failure is dangerous in HIV disease as it may result in diminished treatment efficacy, development of genotypically resistant mutations, viral rebound, and subsequent reduction in HIV treatment options. Despite the importance of adherence in HIV disease, our understanding of factors predictive of adherence in children and adolescents remains incomplete. Prior studies of adherence in children with HIV infection, while often atheoretical, have identified multiple contextual factors associated with adherence, including disease characteristics, features of the medication regimen, and characteristics of the caregiver and family, such as caregiver education and problem-solving skills, caregiver relationship to the child, and child and caregiver stress (Hammani et al., 2004; Martin et al., 2007; Mellins, Brackis-Cott, Dolezal, & Abrams, 2004; Naar-King et al., 2006; Pontali, 2005). Child and adolescent developmental issues, including older age, knowledge of HIV diagnosis, and adjustment to chronic illness have also been implicated, although findings remain inconsistent (Simoni et al., 2007; Williams et al., 2006). Neurocognitive impairment, due to the neuropathological effects of HIV infection, is a significant complication of perinatally acquired HIV infection (Van Rie, Harrington, Dow, & Robertson, 2007). It has been associated with nonadherence in adults with HIV (Hinkin et al., 2004) and may provoke similar risk in children and adolescents. Global or mild cognitive deficits, if present, may impede or delay development of those functional skills essential for adherence, such as understanding and following parental and provider directions, remembering schedules and dosage, and communicating needs effectively. The purpose of this study was to examine cognitive functioning in children and adolescents with HIV, and to evaluate its relationship with medication adherence. We hypothesized that adherence to ART and HAART with PIs will be compromised in the presence of neurocognitive deficits in children and adolescents with HIV infection. We also evaluated potential confounding factors, including demographic characteristics, biological markers of health, medication and adherence factors, and child and family psychosocial characteristics that have been associated with medication adherence in previous investigations.